With a four inch (102 mm) gun in place of her three inch (76 mm) gun, Scorpion set out on her second war patrol on 29 May. On 2 June, she refueled at Midway Island and, on 21 June, she arrived off Takara Jima in the Tokara Gunto. For the next week, she searched for targets in that archipelago in an effort to disrupt shipping on the Formosa-Nagasaki routes. On 28 June, she shifted her hunt to the Yellow Sea and, by 30 June, was off the Shantung Peninsula. On 3 July, she sighted a five-freighter convoy with one escort making its way through the eastern waters of that sea. By 09:55, she had sent torpedoes toward the convoy and dived. As the depth charging began, she struck bottom at 25 fathoms (46 m). Two charges exploded close by. Between 10:02 and 10:06, five more shook her hull. Fearing that she was stirring up a mud trail, her screws were stopped and she settled on the bottom at 29 fathoms (53 m). At 10:08, a chain or cable was dragged over her hull. Four minutes later, her hull was scraped a second time. Immediately underway again, she began evasive course changes and escaped further exploding charges. The hunt continued for over an hour; and, at 11:49, Scorpion came to periscope depth; spied the destroyer 7,000 yards (6.4 km) off; and cleared the area. Postwar examination of Japanese records show that Scorpion scored five hits and sank a 3,890-ton freighter, and a 6,112-ton passenger-cargo ship.
Because of damage received during the depth charging, Scorpion retraced her route through Tokara Gunto; underwent a bomber attack east of Akuseki Jima; and continued on to Midway Island. On 26 July, she arrived back at Pearl Harbor; underwent repairs, conducted training exercises.